Hemodynamic Responses to RLX030 Infusion in Subjects With Acute Heart Failure

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01543854
First received: February 28, 2012
Last updated: August 4, 2014
Last verified: August 2014
  Purpose

This study will assess the hemodynamic effect of RLX030 infusion in subjects with acute heart failure. In addition safety and effects on renal function and biomarkers will be assessed.


Condition Intervention Phase
Acute Heart Failure
Drug: RLX030
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double Blind, Randomized, Parallel Group, Placebo-controlled Study to Evaluate the Hemodynamic Responses to Intravenous RLX030 Infusion in Subjects With Acute Heart Failure

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Peak change from baseline of PCWP (pulmonary capillary wedge pressure) [ Time Frame: baseline, after 8 and 20 hrs treatment ] [ Designated as safety issue: No ]
    Measurements will be made using a Swan-Ganz indwelling catheter

  • Peak change from baseline of CI (cardiac index) [ Time Frame: baseline, after 8 and 20 hrs treatment ] [ Designated as safety issue: No ]
    Measurements will be made using a Swan-Ganz indwelling catheter


Secondary Outcome Measures:
  • Change over time of PCWP (pulmonary capillary wedge pressure) [ Time Frame: During 20 hours of infusion and up to 4 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Measurements will be made using a Swan-Ganz indwelling catheter

  • Change over time of systemic vascular resistance (SVR) [ Time Frame: During 20 hours of infusion and up to 4 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Measurements will be made using a Swan-Ganz indwelling catheter

  • Change over time of pulmonary vascular resistance (PVR) [ Time Frame: During 20 hours of infusion and up to 4 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Measurements will be made using a Swan-Ganz indwelling catheter

  • Change over time of pulmonary arterial pressure (PAP) [ Time Frame: During 20 hours of infusion and up to 4 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Hemodynamic measurements were made using a Swan-Ganz catheter when patients were in a supine position

  • Change over time of pulmonary and peripheral oxygen saturation [ Time Frame: During 20 hours of infusion and up to 4 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Hemodynamic measurements were made using a Swan-Ganz catheter when patients were in a supine position

  • Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to infinity (AUCinf) [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an in dwelling catheter.

  • Pharmacokinetics of RLX030: area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an in dwelling catheter.

  • Pharmacokinetics of RLX030: serum concentration over 20 hours of infusion (C20h) [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an in dwelling catheter.

  • Pharmacokinetics of RLX030: terminal elimination half-life (T1/2) [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an in dwelling catheter.

  • Pharmacokinetics of RLX030: mean residence time (MRT) [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an in dwelling catheter.

  • Pharmacokinetics of RLX030: volume of distribution at steady state following intravenous administration [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    Blood will be collected from an in dwelling catheter.

  • Change over time on calculated creatinine clearance [ Time Frame: During 20 hours of infusion and 4 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Urine samples will be collected for analyses.

  • Change over time in Diuresis [ Time Frame: During 20 hours of infusion and 4 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Urine samples will be collected for analyses.

  • Central aortic systolic pressure-time curve [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms

  • Radial augmentation index-time curve [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: No ]
    A cuff will be used for a brachial blood pressure measurement and a wrist sensor for arterial pulse waveforms

  • Number of patients with adverse events, serious adverse events and death [ Time Frame: During 20 hours of infusion and 24 hours after stop of infusion ] [ Designated as safety issue: Yes ]
    Adverse events will be assessed by signs/symptoms, clinical laboratory and electrocardiographs.


Enrollment: 71
Study Start Date: March 2012
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RLX030
RLX030 as intravenous infusion for 20 hours
Drug: RLX030
Intravenous infusion of RLX030 over 20 hrs
Other Names:
  • serelaxin*
  • *International Nonproprietary Name
Placebo Comparator: Placebo
Matching placebo as intravenous infusion for 20 hours.
Drug: Placebo
Intravenous infusion of placebo over 20 hours

  Eligibility

Ages Eligible for Study:   18 Years to 87 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients hospitalized or requiring admission to hospital for management of acute heart failure within the previous 48 hours.
  • Pulmonary wedge pressure above or equal to18 mmHg determined by right heart catheterization

Exclusion Criteria:

  • Systolic blood pressure below 115 mmHg
  • Significant valvular diseases or arrythmias
  • Acute coronary syndrome in previous 45 days
  • Treatment with mechanical support (intra-aortic balloon pump, endotracheal intubation, mechanical ventilation, or any ventricular assist device)
  • Impaired renal or hepatic function

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01543854

Locations
Argentina
Novartis Investigative Site
Caba, Buenos Aires, Argentina, C1180AAX
Novartis Investigative Site
Buenos Aires, Argentina, B1846BMF
Germany
Novartis Investigative Site
Bad Nauheim, Germany, 61231
Novartis Investigative Site
Berlin, Germany, 10117
Novartis Investigative Site
Dortmund, Germany, 44137
Novartis Investigative Site
Erfurt, Germany, 99089
Novartis Investigative Site
Greifswald, Germany, 17475
Novartis Investigative Site
Halle/'Saale, Germany, 06120
Italy
Novartis Investigative Site
Brescia, BS, Italy, 25123
Netherlands
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Poland
Novartis Investigative Site
Warszawa, Poland, 04-628
Novartis Investigative Site
Wroclaw, Poland, 50-981
Russian Federation
Novartis Investigative Site
Kemerovo, Russian Federation, 650002
Novartis Investigative Site
Moscow, Russian Federation, 127644
Novartis Investigative Site
Moscow, Russian Federation, 121552
Novartis Investigative Site
S.-Petersburg, Russian Federation, 198205
Novartis Investigative Site
Saint Petersburg, Russian Federation, 199106
Novartis Investigative Site
St-Petersburg, Russian Federation, 198013
Novartis Investigative Site
St. Petersburg, Russian Federation, 192242
Novartis Investigative Site
Tomsk, Russian Federation, 634012
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01543854     History of Changes
Other Study ID Numbers: CRLX030A2201, 2011-000833-35
Study First Received: February 28, 2012
Last Updated: August 4, 2014
Health Authority: Germany: BfArM - the National Institute for Drugs and Medical products
Poland: Ministry of Health
Italy: Ministry of Health
Russia: Ministry of Health
Argentina: ANMAT - Ministry of Health

Keywords provided by Novartis:
Heart failure
RLX030
Hemodynamics
Cardiovascular Diseases

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 14, 2014